Preparation and subsequent formulation of a wide range of active pharmaceutical ingredients, in particular protein-based ingredients, typically define certain requirement with respect to the storage stability, homogeneity and ease of handling of the bulk materials used in such preparations and formulations. Allergen products are examples of such bulk materials. Allergen products are often obtained in an aqueous solution, and such aqueous solutions are most often freeze-dried before storage. However, for industrial scale preparation and formulation, freeze-drying is not particularly suitable due to the fact that (i) it is laborious and work-consuming to freeze-dry large quantities of material, (ii) freeze-drying requires expensive equipment; (iii) reconstitution of the product is often laborious and time-consuming.
WO 00/06179 (Eli Lilly & Co.) discloses a method of processing an aqueous solution of activated protein C (aPC) into a state suitable for storage, handling and recovery. The method comprises the steps of (i) dividing the solution into drops, and (ii) freezing the drops into cryogranules using a stream of liquid nitrogen. The stream of liquid nitrogen and cryogranules are subsequently led to a conveyor that holds back the cryogranules and allows the liquid nitrogen to fall through. The cryogranules can be collected and stored in a sealed container. The cryogranules can afterwards be used as starting material for commercial scale production of a pharmaceutical composition. The preparation of the cryogranules, however, requires complicated equipment, e.g. a cryogranulation unit including the before-mentioned conveyor that is difficult to maintain and clean. Furthermore, implementation of GMP protocols for using a cryogranulation unit is laborious and time-consuming.
WO 03/20959 (BTF Pty Ltd) discloses a method for the preparation of products containing a quantum of bioparticles, wherein the method i.a. comprises the steps of forming a solid body by placing a droplet in a container that comprises a cryogenic liquid so as to form a frozen body, subsequently drying (e.g. freeze-drying) the frozen body to form a substantially dry solid product within the container, and, if desired, capping or sealing the container for storage and transport of the product.
In spite of the above, there is still a need for a more rational process for industrial scale preparation of batches of active pharmaceutical ingredients that are suitable for handling and storage.